Abstract

Introduction - A recent study comparing
heterosexual men with and without confirmed sexually
transmitted diseases (STDs) in an urban STD clinic showed
that uncircumcised men were less likely than circumcised
men to have genital wart detectable by clinical examination
(adjusted odds ratio 0.7, 95% confidence interval 0.4,
0.9). Based on these initial findings we hypothesised that
the appearance and anatomic distribution of genital warts,
and possibly treatment response, may be different for
circumcised and uncircumcised men.

Methods - The anatomic location,
appearance, number of warts, and response to treatment was
investigated through review of medical records of 459
heterosexual men with genital warts detected in 1988.

Results - Age- and race-adjusted
estimates indicated that among men with genital warts,
warts were detected much more commonly on the distal penis
- that is, the corona, frenulum, glans or urethrul meatus -
among uncircumcised men (26%) than among circumcised men
(3%) (OR 10.0, 95% CI 3.9, 25.7). Where the appearance was
specified, warts were more often described as condylomatous
in uncircumcised men and slightiy more often as papular in
circumcised men. No significant difference between
circumcised and uncircumcised men was seen in the number of
return visits to the clinic for persistent warts after
treatment with liquid nitrogen: 2.2 visits for 19
uncircumcised men and 2.3 visits for 149 circumcised
men.

Conclusion - Circumcised men were more
likely than uncircumcised men to have genital warts, but
when present, warts were more often located on the distal
portion of the penis among uncircumcised men. This paradox
is not understood, but could reflect either non-specific resistance to proximal penile
warts conferred by the foreskin, or heightened
susceptibility to various HPV types in uncircumcised men,
some of which may confer subsequent immunity to genital
warts.

(Genitourin Med
1993;69:262-264)

Introduction

Previous studies have suggested that genital
warts occur more commonly among uncircumcised men than among
circumcised men.1-3 However, in
a recent study using the medical records of 2776 heterosexual
men attending the Seattle-King County Sexually Transmitted
Disease Clinic at Harborview Medical Center, the prevalence
of genital warts among cirucumcised men (17.6%) exceeded that
of uncircumcised men (11.0%, (p < 0.001).4 The relationship persisted after
adjusting for age, race, other STDs, place of residence, and
the number of sexual partners in the previous month Also,
circumcised men were more likely than uncircumcised men to
report a history of previous warts (12.9% vs 7%, p <
0.001). In contrast, uncircumcised men were more likely to
have syphilis (OR 4.0, 95% CI 1.9. 8.4) and gonorrhea (OR
1.6, 95% CI 1.2, 2.2). Our results may differ from those of
previous studies because of our restriction to heterosexual
men and our adjustment for more confounding variables. In
view of these results, the present analysis was undertaken to
characterise differences in the anatomic location,
appearance, number, and apparent treatment response of
genital warts based on circumcision status in this
population.

Methods

A review of heterosexual men seen in the
Seattle-King County STD clinic in Seattle, Washington from
January 1988 to December 1988 identified 463 men diagnosed
clinically with genital warts. Details of this study have
been reported.4 Briefly,
information was available on subject demographic
characteristics, symptoms, sexual history, prior STDs, and
clinical and laboratory diagnostic findings. Circumcision
status was identified and recorded by the clinician.

For the present study, the medical records of
459 of the 463 men given a diagnosis of genital warts during
1988 were reviewed and information was abstracted on the
location, number, and appearance of the exophytic warts (the
medical records of four subjects were not available). The
location of warts was categorised as distal penis (including
the glans, coronal sulcus, urethral meatus, and frenulum),
proximal penis (including the shaft and base of the shaft),
both (distal and proximal), other (including scrotum, thighs,
perianal area, and inguinal fold), or location not recorded.
Four uncircumcised subjects had warts on the foreskin and
were excluded from the analysis. Multiple locations that
included sites other than the penis were coded on the basis
of the location of the penile warts, that is, a subject with
warts on the glans and the inguinal fold was classified as
distal penis. The appearance of warts was categorised as
condylomatous papular other (verruca vulgaris), or appearance
not recorded. The number of warts was categorised in three
groups: 1, >1, or number not recorded.

Demographic and sexual characteristics of
uncircumcised and circumcised men were compared. The number,
anatomic distribution, and appearance of genital warts was
also compared based on circumcision status. Among men with
genital warts, age- and race-adjusted odds ratios relating
circumcision status with the location, appearance, and number
of warts were calculated by logistic regression
analysis.5 The response to
treatment could not formally be compared in circumcised and
uncircumcised men; clinic patients were generally advised to
return for repeated treatment as long as warts persisted, but
complete follow-up of all 459 men until the warts had
resolved was not attempted by the clinic staff. Therefore, as
a surrogate for treatment response, we compared the number of
follow-up clinic visits at which persistent warts were
detected among the 345 men treated with liquid nitrogen
applications at the initial clinic visit. All analyses were
done using SAS.

Results

Among heterosexuals with genital warts (Table
1), circumcised men were more likely than uncircumcised men
to be 30 years or older, (33.7% vs 21.7%, p =0.05), white,
(76.3% vs 45.7%, p < 0.007), and to report a history of
warts (39.5% vs 23.9%, p < 0.01). No major differences
were noted between cc groups with respect to the number of
sexual partners in the previous month, and approximately
two-thirds of both groups reported symptoms of genital
lesions when specifically queried about lesions prior to
examination. The figure shows that the penile shaft,
including the base of the shaft, was the most common location
for genital warts in both circumcised and uncircumcised men.
However, circumcised men were more likely to have warts in
this location (77% vs 61%, p < 0.001), whereas
uncircumcised men were much more likely to have distal penile
warts (26% vs 3%, p < 0.0001). Age- and race-adjusted
results (Table 2) comparing the presence of distal penile
warts wth proximal penile warts also indicate that distal
warts are more likely in uncircumcised men (OR 10.0, 95% CI
3.9, 25.7). The presence of multiple wart lesions was
unrelated to circumcision status. Condylomas were more likely
than papules in uncircumcised men (OR 2.5, 95% CI 0.8, 7.6),
but the appearance of warts was only specified for a small
subset of subjects.

Approximately 50% of uncircumcised and
circumcised subjects initially treated with liquid nitrogen
for their genital warts did not return to the clinic for
follow-up visits (Table 3). Of those who returned, the mean
number of visits with warts detected was virtually identical
between circumcision groups: 2i2 visits for uncircumcised men
and 2.3 visits for circumcised men.

Discussion

This review of medical records of heterosexual
men found to have genital warts at our STD clinic in 1988
shows that warts were more likely to be distal, and to have a
condylomatous appearance, among uncircumcised men than among
circumcised men. However, the response of genital warts to
liquid nitrogen application appeared comparable in the two
groups.

In the present study, the foreskin itself was
seldom affected, with only four subjects having warts on the
inner or outer surface of the foreskin. These four subjects
were excluded from the analysis since circumcised men do not
have a comparable anatomic site at risk for infection; their
inclusion would have elevated the positive relationship
between uncircumcised status and distal penile warts. A
possible concern is the higher proportion of circumcised men
(9%), compared with uncircumcised men (2%) who did not have
the location of wart lesions recorded in their medical
record. It could be argued that if most, or all, of these
circumcised men actually had distal warts, the positive
relationship between the presence of a foreskin and distal
penile warts would disappear. However, even if we
conservatively assume that all the circumcised men with
unspecified wart locations (n = 38) had distal penile warts,
there would still be a higher proportion of uncircumcised men
with genital warts on the distal penis (OR 2.7, 95% CI 1.2,
5.4).

The relationship between the appearance of warts
and circumcision status in this population is consistent with
a study from St. Thomas' Hospital, which indicated that
fleshy hyperplastic warts, or classic venereal warts, were
most common on the glans and the inner lining of the foreskin
among uncircumcised men.3 The
anatomic distribution of genital warts found in the present
study, and in studies from St. Thomas' Hospital3 and the Mayo Clinic,6 are compared in Table 4. In contrast
to both the present study and the Mayo Clinic study, distal
penile warts were more common than proximal waits in the St
Thomas' Hospital study. This discrepancy could be due in part
to the high percentage of men who were uncircumcised in the
St. Thomas' Hospital study (79%).

Table 4 Comparison of the anatomic distribution
of genital warts in men seen at the STD clinic,
Seattle Washington 1988 and St. Thomas' Hospital,
London 1967-1970, and at the Mayo Clinic6,
Rochester, Minnesota 1950-1978.

In contrast to our findings, a Canadian Army
study found that uncircumcised status was more common among
active duty men with warts than among recruits without
warts.1 However, differences
between these two groups of Canadian men in age, sexual
activity, and other factors could have strongly influenced
the study results. Age-adjusted analyses from the Public
Health Department Special Treatment Clinic in Perth,
Australia, suggested uncircumcised men were more likely than
circumcised men to have warts (OR 1-5, 95% CI 1-0,
2-4).2 Discrepancies with our
results could be due to our restriction to heterosexual men,
our adjustment for confounding factors, and any systematic
differences in health seeking behavior between circumcised
and uncircumcised men residing in the two countries.

In summary, among heterosexual men at our STD
clinic, uncircumcised men had a lower
prevalence of genital warts than circumcised men, yet
when warts occurred in uncircumcised men, they were more
likely to be distal warts under the foreskin. It is possible
that the less cornified epithelium of the distal penis within
the preputial sac has increased susceptibility to HPV,
including those types causing condylomas. A higher incidence
of early subclinical, subpreputial HPV infection could
promote immunity to subsequent penile condylomata. The series
of men at our STD clinic may include a high proportion who
have already expericnced such an infection and acquired some
immunity. Alternatively, the presence of
the foreskin may confer nonspecific protection of the
proximal penis from acquisition of HPV infection.